Endocannabinoid Regulation of the Hypothalamo-Pitiutary-Adrenal Axis

Beat Lutz
Institute of Physiological Chemistry and Pathobiochemistry,
Johannes Gutenberg-University Mainz, GERMANY

The endocannabinoid system has recently emerged as an important modulator in a plethora of behavioural responses to both internal and external stressors under physiological and pathophysiological conditions.

In particular, the notion has been put forward that the endocannabinoid system is an endogenous system in order to stabilize and to maintain the body’s homeostasis after stressors may have induced an imbalance.

Endocannabinoids and cannabinoid receptor type 1 (CB1 receptors) are present at most if not all levels of the hypothalamic-pituitary-adrenal (HPA) axis, and there is good evidence that CB1 receptor activation is able to modulate ACTH and corticosterone secretion. At the cellular level, endocannabinoids are able to regulate synaptic transmission by a mechanism called depolarization induced suppression of excitation (DSE) and of inhibition (DSI). Endocannabinoids are also able to regulate intracellular signaling cascades that subsequently may regulate the secretion of stress hormones. These features, together with behavioural assays and (neuro)endocrine investigations on mouse model systems lacking CB1 receptors and on rodents treated with CB1 receptor antagonist provide interesting new insights into the role of the endocannabinoid system on the regulation of the HPA axis and, consequently, also on stress and anxiety . Therefore, the endocannabinoid system may constitute a promising new therapeutic target in various disorders with imbalances in the HPA axis.
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Still politicians pretend there is no medical foundation to self administration of THC, and continue to lock people up.
Criminalised cannabis is a health intervention with double jeopardy. (the minister of justice acts on the warrant of the minister of health)

The biopsychosocial consequences are self evident. Classified cannabis IS the imediment to achieving best practice public health.

Placing it in Class D is the expeditious remedy.

The right to possess herbals would be a barren right without the right to the business models that included cultivation or manufacture, transport, processing, quality control , storage and handling, sale and exchange. The crown even provides funding for health promotion messages.(it also collects GST on high ‘value added’ margin )

The above Lutz abstract is a complete validation of the harm reduction models proposed by Colorado University (Boulder) Biology Chair, Dr (Assoc Prof) Robert Melamede mentioned elsewhere in this blog. i.e. Harm reduction the cannabis paradox.

Also see The Endocannabinoid System: Friend or Foe?
February 15, 2006, Host: Dr. Kenneth Mackie
and 5th Forum of European NeuroScience, Vienna, July 2006

and

Advancing the Management of Cardiovascular and Metabolic Risk Factors: The Role of the Endocannabinoid System.

More recently NAEs have been shown to be part of the endocannabinoid signaling system. Recent investigation has shown that cannabinoid drugs (active ingredient D9-THC) act via membrane bound receptors (G-protein coupled) and NAEs act as endogenous ligands that react with the receptors CB1 and CB2. Anandamide (NAE20:4) binds to and activates CB1 receptors in neurons, initiating an intracellular signaling cascade that leads to changes in ion flux at the plasma membrane

Endocannabinoid Signaling in the brain: role of N-acylethanolamine metabolism

Blair Anderson
ph (643) 389 4065 cell 027 26572109

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Man Dies After Being Tasered By Police

The suspect was displaying what he called “assaultive behavior” and did not stop when ordered – the officer feared for his life when the man turned toward him.

Yeah Right!

The (August 5th) incident started with a drug bust at a field in Louisville. Police said Ryan Wilson, 22, admitted to growing marijuana before running away from police. Officers chased Wilson and Officer John Harris eventually confronted him and used a 50,000 volt TASER.

Investigators said Harris immediately noticed something was wrong. “As soon as the individual went into convulsions, the officer, himself, started CPR on the individual and called for the ambulance to respond,” said Sgt. Bill Palmer with the Lafayette Police Dept. “So, he was doing CPR along with another officer when the ambulance arrived.”

The Boulder County coroner was conducting an autopsy to determine why a man died.

It is my guess the scope of the coronal inquiry will not include the required policy analysis… nor get at real the truth of the taser’s application, time to medically intervene or why there seems to be tension between the Police claim of “assaultive behavior” and the suspect running away…

This tragedy will not allay legitimate public fears related to taser use, will not inspire confidence in police and may indeed bring even the coronal inquiry into disrepute. (let alone address the family’s angst and anger and this extra-judicial capital punishment – see video )

All over ‘some pot’ that in Denver City down the road, is, by public treaty and vote given a low priority.

So, then… where are Denverites going to grow, who is going to grow and how it will arrive into the hands of those who are the consumers?

And that all presumes this now dead young man wasn’t growing for his own use. The right to possess is a barren right without the right to cultivate, store, trade and consume.

The malfunction was not the taser rather the grotesque enforcement of a law in wholesale disrepute.

/Blair Anderson

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Good news: Prohibitionism can be cured…

Seriously, this is no joke, soon there will be a pill for intransigence ….

Now, how do we get it into JimA without him noticing?

[Harvard School of Medicine] Researchers hope to develop medications that can mitigate the adverse affects of the protein on cognitive functioning, as presented by a behavioral, affective and cognitive sequelae that includes intellectual rigidity and incuriosity, self-righteousness, the introjection of conventional and traditional moral codes that support unrealistic feelings of moral superiority, the amoral, utilitarian use and/or abuse of such moral codes when it serves their individual purposes, the use of social dominance and aggression in enforcing such conventions upon others, educational deficits despite lackluster efforts to acquire credentialing, and aversion to logic, otherwise diagnosed as dementia among geriatric populations.

Would it be seditious to suggest we should somehow mickyfinn the Coffee at Belamy’s?

Blair Anderson
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Epilepsy and other neurodegenerative diseases

Medical Research News

Source: News-Medical.Net Australia

Endocannabinoid System Controls Key Brain Circuits

The same brain machinery that responds to the active substance in marijuana provides a central “on-demand” protection against seizures, researchers have found. The “endocannabinoid” system might constitute a prime target for drugs against seizures of epilepsy and other neurodegenerative diseases.

“In conclusion, our study reveals a mechanism through which the endocannabinoid system is able to provide on-demand protection against acute behavioral seizures. “

/Blair Anderson

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MARIJUANA AND THE BRAIN

Cannabis divides people: some see it as unfairly demonised, others as a medical catastrophe in the making. Elizabeth Finkel breaks through the panic and the hype to find out what science has to say.

Actually she makes a fair sized fist of it too… Dr. Alex Wodak, Wayne Hall, Professor Miron and more – every prohibitor should read this insight. / Blair Anderson.

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New Directions in Drug Education

Recent chatter about random drug testing all youths is attracting attention despite any evidence it has worked anywhere. This is just so much more moral panic. I don’t see public health officials lining up to randomly test for HIV, Chlamydia, Gonorrhea or Pregnancy or Nicotine despite obvious harms.

Current thinking in education best practice has moved beyond the idea we can just inoculate these kids against drug use with a dose of fear and intolerance.

Suspicion-less pee in a bottle good kid collect $200, bad kid go to Jail has been found wanting by the San Francisco Medical Society, the Office of the Mayor of San Francisco, their Department of Public Health, County Department of Health and Human Services, the International Institute for Restorative Practices, the Drug Policy Alliance and California State Assembly member Jackie Goldberg. All of whom, along with Educators for Sensible Drug Policy share common concerns for our young folk.

It is Time To Talk before we ban our way out of this problem [of course, absent any evidence any of it works] and crucially, without the informed consent of parents and young folk. (no decision about us without us.)

A well titled “New Directions in Drug Education and School Discipline” conference in California this October (with continuing education credits) explores realistic, pragmatic, and cost-effective strategies for implementing drug education and effective disciplinary practices in secondary schools.

Masters, Principals, Trustees and Parents can learn how to adopt culturally appropriate real-life interactive, participatory high school drug education [and assistance programs]. I suspect San Francisco mayor Gavin Newsom supports restorative Beyond Zero Tolerance practices in California high schools because it works.

(which begs the question, why wouldn’t ‘beyond zero tolerance’ work for adults.? Or is this a clue as to why draconian testing of kids is required, to prove cannabis is dangerous? Who too? kids let alone adults, don’t believe it’s dangerous, it’s only class C anyway! We have a system that suggests Class A must mean really** good!)

Author, Professor Skager was here late April, he lauded our indigenous restorative practices. I think it would be a good idea to bring him back to NZ, but, if you missed him – download the booklet and view the conference who’s who at BEYONDZEROTOLERANCE.ORG.

Our national record of suspension and expulsion is a poor measure of success but then there has been no “ESSENTIAL” cost benefit analysis on current policy outcomes. [It was budgeted for, ten years ago.]

The culture of intolerance and fear of self-examination is all on the prohibitor’s watch, where as the evidence base is on ours.

* “It’s Essential” – Dr Paul Hutchison, MP [Raglan]. National Party Conference, (private conversation) Christchurch 2006

** Science and Technology Select Committee report on Drug Classification (August 2006), Home Office. Gt.Britain

Week ending, 18th August.

Penn and Teller, Weed = 2, Prohibition nil.

Blair Anderson
643-3894065

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Bong ban is NOT Harm Minimisation

The “bong ban” was introduced by the Minister of Health as part of a “harm reduction” based strategy, midway through the year 2000…see 08 Jul 1999: Bong ban is NOT Harm Minimisation (and other useful analysis)

Now Drug Czar Anderton wants to get tough on paraphernalia !

Whaaa !! I bet he doesn’t even know what the word means. Not, “Miscellaneous articles or personal possessions”, I mean harm minimisation!

Blair Anderson
http://mildgreens.com

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EFSDP: Drug Crusaders, Listen Up

Aug 15
Editor
Nelson Daily:

Letter writer Nicole Lorusso employs a common tactic of the drug war cheerleaders. First erect a straw man of grotesque proportions and then proceed to tear it back down again (Drug Crusaders, Listen Up, Aug 15) I am not aware of a single credible drug law reform activist that advocates willy-nilly use of cannabis by children. Teen age drug abuse is bad. Bad for families, bad for society and most assuredly bad for children. We’re all in agreement.

But it does not automatically follow that if teen age drug abuse is bad, well then Prohibition must be good.

I am also an educator, a school counselor in this case.   And for every horror story Ms. Lorusso can conjure up involving teenagers using pot, I can recite two more where children were grievously harmed by the excesses of the Drug War, Inc. Children snatched from loving families after a few marijuana plants were discovered behind the family garage during the annual fly-over. Children duped into informing on their parents by that nice Officer Friendly from DARE. Children traumatized when the front door of the family home was kicked in at 4:00 a.m. by ninja clad thugs–talk about your narco terrorism!

Ms. Lorusso’s assertion not withstanding, our highest goal is not about preserving the dignity of adult cannabis consumers. It’s about preserving the traditions and values of a free, democratic society. A society that respects its own citizens right to self determination and to be protected from an over reaching and ever more intrusive state apparatus. It’s about saying, no, to a liberal, nanny state government.

Legalize, regulate, tax, control. There is a better way.

Greg Francisco, M.A.
Educators for Sensible Drug Policy, www.efsdp.org
32323 M-43
Paw Paw, MI  49079
USA
(269) 628-4340

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Blair Anderson
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Sports Disputes Tribunal let Dickel off lightly says Doc.

Sports Drugs Agency head Dr Dave Gerrard says the Sports Disputes Tribunal let Dickel off lightly. He says it provides a bad example to young athletes. Gerrard says Dickel is a silly man for considering that the use of cannabis is in any way fitting for a role model in sport.

http://www.newstalkzb.co.nz/newsdetail1.asp?storyID=101663

To say nothing of alcohol… some folk doing the critical thinking here might consider the ramifications of every kid who smoked a recreational joint aspiring to play even half as well as Mark Dickel.

Mark clearly has no ‘problem’ with his drug use other than the hypocritical double standards of sports administrators lining up for liquor sponsorship and vendign rights at venues.

The problem lies with a drug agency that pretends cannabis is harmful while for tens of thousands of young people alcohol will manifest tragedy and expensive life changing outcomes. Such outcomes pale beside role model Dickel’s seemingly ‘responsible, recreational use’ of the herb.

Profesional urine tester, Dr. Dave detected cannabis ‘at five weeks’. It has been my experience that the small minority of athletes who do choose to use drugs are much more likely to switch from cannabis detectable for weeks, to alcohol and methamphetimine both detectable for mere hours.

Could the Doctor’s first do no harm principals be tested for ‘silly’ or ‘success’?

The effort and expendature put into Ministry of Health ‘anti-labeling’ efforts using notable sports stars didnt stop TV3’s use of ‘Dopey Dickel’ footage accompanied by a hit tune that mocked prohibitors.

Doubtless TV3 didn’t notice their deilvery of pure prejudice dopey drug policy is at all levels just harm maximisation.

Were cannabis, a recognised ‘safe’ therapeutic ‘known to man’ rightly dropped from the sports performance enhancing drugs schedule the unintended consequence might usefully engage youth in healthy extra-curricular and stimulating sports activities but also result in a few more unemployed urine checkers.

/Blair Anderson

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THC Blocks Alzheimer’s Plaque Formation

THC Blocks Alzheimer’s Plaque Formation

Old hippies who haven’t toked for decades might come back to the stoner life. Marijuana active ingredient tetrahydrocannabinol blocks the formation of beta amyloid plaques which are suspected as a cause of Alzheimer’s disease.

LA JOLLA, CA, August 9, 2006 – Scientists at The Scripps Research Institute have found that the active ingredient in marijuana, tetrahydrocannabinol or THC, inhibits the formation of amyloid plaque, the primary pathological marker for Alzheimer’s disease. In fact, the study said, THC is "a considerably superior inhibitor of [amyloid plaque] aggregation" to several currently approved drugs for treating the disease.

The study was published online August 9 in the journal Molecular Pharmaceutics, a publication of the American Chemical Society.

According to the new Scripps Research study, which used both computer modeling and biochemical assays, THC inhibits the enzyme acetylcholinesterase (AChE), which acts as a "molecular chaperone" to accelerate the formation of amyloid plaque in the brains of Alzheimer victims. Although experts disagree on whether the presence of beta-amyloid plaques in those areas critical to memory and cognition is a symptom or cause, it remains a significant hallmark of the disease. With its strong inhibitory abilities, the study said, THC "may provide an improved therapeutic for Alzheimer’s disease" that would treat "both the symptoms and progression" of the disease.

The development of better tests for amyloid plaque formation probably will provide the ability to predict the development of Alzheimer’s many years in advance of obvious symptoms. For people who face the threat of losing their memory 10 years hence if THC can prevent or delay that outcome use of THC might be worth it. Though quite a few people won’t want to go through every day of their lives high on THC.

THC works better than commercial drugs currently on the market.

"When we investigated the power of THC to inhibit the aggregation of beta-amyloid," Janda said, "we found that THC was a very effective inhibitor of acetylcholinesterase. In addition to propidium, we also found that THC was considerably more effective than two of the approved drugs for Alzheimer’s disease treatment, donepezil (Aricept ®) and tacrine (Cognex ®), which reduced amyloid aggregation by only 22 percent and 7 percent, respectively, at twice the concentration used in our studies. Our results are conclusive enough to warrant further investigation."

Alzheimer’s is a terrible disease. It gradually robs you of your identity. People who face the prospect of losing their memories should be allowed a great deal of latitutde in terms of what they can do to protect themselves from that fate. I expect drugs, antibodies, and vaccines will all come to market in the next 10 years that stop and reverse beta amyloid plaque formation. Use of THC for this purpose will be transitory at best. But will any government even allow clinical trials of its effectiveness against Alzheimer’s?

By Randall Parker at 2006 August 12

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Blair Anderson
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